The general anesthetics have many effects on the nervous system. In addition to producing anesthesia of the central nervous system, they also exhibit prominent effects on the peripheral nervous system. Many anesthetics depress neuromuscular transmission by an action on the post- junctional membrane. Depressant effects also been observed for nicotinic transmission in sympathetic ganglia, however, the ionic mechanism of ganglionic depression has never been investigated. Electrophysiological techniques will be used in this project to analyze the actions of general anesthetics on synaptic transmission in the ganglion. The effects of ether, halothane, methoxyflurane, nitrous oxide, cyclopropane and barbiturates on hamster ganglia will be investigated initially with extracellular techniques. The dose-effect relationship will be determined for each anesthetic on the nicotinic e.p.s.p. (excitatory postsynaptic potential), muscarinic e.p.s.p. and i.p.s.p. (inhibitory postsynaptic potential) with postganglionic and sucrose-gap recording techniques. The concentrations of anesthetic will be accurately measured from a sample of bathing solution by gas chromatographic techniques. Specific effects of each anesthetic will be explored with intracellular techniques to distinguish, firstly, between effects on 1) The ganglion cell membrane and 2) The ganglionic synapse. Then the ionic mechanism of each effect will be established. In this way it will be possible to determine if all anesthetics act by a similar mechanism in depression of nervous activity or whether the variation of chemical structure of anesthetics is accompanied by a variation of mechanism in producing blockade.